Advanced Science Research Center at the Graduate Center, Neuroscience Initiative, City University, New York, United States.
Department of Neuroscience, Icahn School of Medicine, New York, United States.
Elife. 2019 Aug 13;8:e40855. doi: 10.7554/eLife.40855.
Exposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behavior ('susceptible') and those who escaped the deleterious effect to stress ('resilient'). Myelin protein content in the nucleus accumbens was reduced in all mice exposed to stress, whereas decreased myelin thickness and internodal length were detected only in the medial prefrontal cortex (mPFC) of susceptible mice, with fewer mature oligodendrocytes and decreased heterochromatic histone marks. Focal demyelination in the mPFC was sufficient to decrease social preference, which was restored following new myelin formation. Together these data highlight the functional role of mPFC myelination as critical determinant of the avoidance response to traumatic social experiences.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
暴露于压力会增加出现情绪障碍的风险。虽然有一部分个体对压力表现出易感性，但其他人则具有弹性，但这些行为差异的分子基础尚不清楚。使用慢性社交挫败应激模型，我们在表现出社交回避行为（“易感”）和逃避应激不良影响的小鼠（“有弹性”）之间发现了髓鞘形成的区域特异性差异。暴露于应激的所有小鼠的伏隔核髓鞘蛋白含量降低，而只有易感小鼠的内侧前额叶皮质（mPFC）检测到髓鞘厚度和节间长度降低，成熟少突胶质细胞减少，异染色质组蛋白标记减少。mPFC 中的局灶性脱髓鞘足以降低社交偏好，而新髓鞘形成后可恢复社交偏好。这些数据共同强调了 mPFC 髓鞘形成作为对创伤性社交体验回避反应的关键决定因素的功能作用。
本文经过编辑过程，作者决定如何处理同行评审中提出的问题。审稿人的评估是所有问题都已得到解决（见评审意见）。
